NHWD-870通过上调PI3K/AKT信号通路保护肾脏免受缺血/再灌注损伤的影响(实验研究)。
NHWD-870 protects the kidney from ischemia/reperfusion injury by upregulating the PI3K/AKT signaling pathway (experimental study).
发表日期:2023 Jun
作者:
Saba Sahib Younis, Fadhaa Abdul Ameer Ghafil, Sahar Majeed, Najah Rayish Hadi
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
肾缺血再灌注损伤是一种临床上严重的疾病,如果管理不当可能会导致致命的预后。NHWD-870是一种已知的Brd4抑制剂,具有抗癌的特性,并表现出抗氧化、抗炎和抗凋亡的效果,表明其具有保护肾组织和减轻缺血损伤的潜力。我们旨在通过研究其在大鼠肾缺血再灌注损伤模型中的抗凋亡、抗炎和抗氧化特性,评估NHWD-870的潜在肾保护作用。将雄性Wistar Albino大鼠(n=24)随机分为四组:假手术组、对照组、载体组和NHWD-870组。对照组经历双侧肾缺血30分钟,然后再灌注2小时,而假手术组只进行腹腔镜手术,不进行缺血再灌注诱导。载体组注射DMSO,NHWD-870组在重复对照组协议前24小时口服3mg/kg NHWD-870。在再灌注后采集血样进行血尿素氮(BUN)和血清肌酐(SCr)分析。使用ELISA方法评估肾组织中的IL-1B、BCL-2、PGF-2和PI3K/AKT信号通路。通过组织病理学分析评估小管损伤程度。与对照组和载体组相比,NHWD-870治疗改善了肾功能和组织学保护。NHWD-870组的BUN、SCr、IL-1B、BCL-2和PGF-2水平在肾组织中显著改善(p<0.05)。此外,PI3K/AKT信号通路显著上调(p<0.01),NHWD-870组的小管损伤程度减轻。NHWD-870在减轻大鼠肾缺血再灌注损伤引起的肾损伤方面表现出显著的肾保护效果。这些效果可能归因于抗凋亡特性,即抗凋亡蛋白Bcl-2水平增加,并通过上调PI3K/AKT信号通路降低氧化应激标志物PGF-2,以及减少炎症标志物IL-1B。©2023医学与生活杂志。
Renal ischemia-reperfusion injury is a critical clinical condition with a potentially fatal prognosis if not adequately managed. NHWD-870, a known Brd4 inhibitor with anti-cancer properties, exhibits additional attributes such as antioxidant, anti-inflammatory, and anti-apoptotic effects, suggesting its potential to preserve renal tissue and mitigate damage during ischemic insults. We aimed to assess the potential nephroprotective effect of NHWD-870 by investigating its anti-apoptotic, anti-inflammatory, and antioxidant properties in a rat model of renal ischemia-reperfusion injury. Male Wistar Albino rats (n=24) were randomly assigned to four groups: sham, control, vehicle, and NHWD-870. The control group experienced bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion, while the sham group underwent a laparotomy without ischemia-reperfusion induction. The vehicle group received a DMSO injection, and the NHWD-870 group was administered 3mg/kg NHWD-870 orally 24 hours before repeating the control group protocol. Blood samples were collected after reperfusion for blood urea nitrogen (BUN) and serum creatinine (SCr) analysis. ELISA method was used to assess IL-1B, BCL-2, PGF-2, and PI3K/AKT signaling pathways in renal tissue. Tubular injury severity was evaluated through histopathological analysis. NHWD-870 treatment improved renal function and histological preservation compared to the control and vehicle groups. BUN, sCR, IL-1B, BCL-2, and PGF-2 levels in renal tissue were significantly improved in the NHWD-870 group (p<0.05). Furthermore, the PI3K/AKT signaling pathway was significantly upregulated (p<0.01), and tubular injury severity was reduced in the NHWD-870 group. NHWD-870 demonstrated substantial nephroprotective effects in reducing renal damage induced by ischemia-reperfusion injury in rats. These effects may be attributed to the anti-apoptotic properties, as indicated by increased levels of the anti-apoptotic protein Bcl-2, and the reduction in oxidative stress marker PGF-2 through upregulation of the PI3K/AKT signaling pathway, along with the decrease in the inflammatory marker IL-1B.©2023 JOURNAL of MEDICINE and LIFE.